The identification and quantitation of specific human cytotoxic effector cells are basic for the understanding of the immune response to alloantigens, intracellular infectious agents and tumor antigens, and might acquire clinical relevance for the evaluation of the patient's immune status. We propose a systematic approach to some aspects of the study of cell-mediated cytotoxicity (CMC) in humans. The main specific aims will be: 1) To analyze the cell population(s) acting as effector in different types of CMC (immune, spontaneous, antibody-dependent, lectin induced, etc). 2) To study the possible interference of non-specific cellular and humoral factors in tests directed to measure the activity of a single effector cell population. 3) To analyze the lytic mechanism induced by the various types of effector cells and the differential requirements for induction of cytotoxicity. 4) To develop CMC tests (following in vivo or in vitro sensitization) against virus infected or transformed cells. 5) To analyze the possibility of restriction of the response to viral and tumor antigens by the HL-A antigens and the possible relationship between viral and tumor surface antigens and histocompatibility antigens. 6) To investigate the ability of human tumor antigens expressed on somatic cell hybrids to induce a cellular immune response in vivo (immunizing experimental animals) and in vitro.